A genome-wide linkage scan of bipolar disorder in Latino families identifies susceptibility loci at 8q24 and 14q32

Suzanne Gonzalez, Cynthia Camarillo, Marco Rodriguez, Mercedes Ramirez, Juan Zavala, Regina Armas, Salvador A. Contreras, Javier Contreras, Albana Dassori, Laura Almasy, Deborah Flores, Alvaro Jerez, Henriette Raventós, Alfonso Ontiveros, Humberto Nicolini, Michael Escamilla

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

A genome-wide nonparametric linkage screen was performed to localize Bipolar Disorder (BP) susceptibility loci in a sample of 3757 individuals of Latino ancestry. The sample included 963 individuals with BP phenotype (704 relative pairs) from 686 families recruited from the US, Mexico, Costa Rica, and Guatemala. Non-parametric analyses were performed over a 5cM grid with an average genetic coverage of 0.67cM. Multipoint analyses were conducted across the genome using non-parametric Kong & Cox LOD scores along with Sall statistics for all relative pairs. Suggestive and significant genome-wide thresholds were calculated based on 1000 simulations. Single-marker association tests in the presence of linkage were performed assuming a multiplicative model with a population prevalence of 2%. We identified two genome-wide significant susceptibly loci for BP at 8q24 and 14q32, and a third suggestive locus at 2q13-q14. Within these three linkage regions, the top associated single marker (rs1847694, P=2.40×10-5) is located 195 Kb upstream of DPP10 in Chromosome 2. DPP10 is prominently expressed in brain neuronal populations, where it has been shown to bind and regulate Kv4-mediated A-type potassium channels. Taken together, these results provide additional evidence that 8q24, 14q32, and 2q13-q14 are susceptibly loci for BP and these regions may be involved in the pathogenesis of BP in the Latino population.

Original languageEnglish (US)
Pages (from-to)479-491
Number of pages13
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume165
Issue number6
DOIs
StatePublished - Jan 1 2014

Keywords

  • Bipolar disorder
  • Central-American
  • Family studies
  • Genetics
  • Mexican
  • Mexican-American

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Gonzalez, S., Camarillo, C., Rodriguez, M., Ramirez, M., Zavala, J., Armas, R., Contreras, S. A., Contreras, J., Dassori, A., Almasy, L., Flores, D., Jerez, A., Raventós, H., Ontiveros, A., Nicolini, H., & Escamilla, M. (2014). A genome-wide linkage scan of bipolar disorder in Latino families identifies susceptibility loci at 8q24 and 14q32. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 165(6), 479-491. https://doi.org/10.1002/ajmg.b.32251